The interstitial cells of Cajal (ICC) are found in a number of differe
nt locations in the gastrointestinal tract, where they form close asso
ciations with both muscle cells and nerve terminals. In this study we
examined the embryological origin of ICC in the mouse intestine to det
ermine whether they arise from the neural crest or from the intestinal
wall. Segments of intestine were removed from embryonic mice either b
efore or after the arrival of neural crest cells (the precursors of en
teric neurons and glial cells) and transplanted under the renal capsul
e of host (adult) mice and allowed to develop for 18-41 days. In the m
ouse intestine, antibodies to c-kit protein selectively label ICC at a
variety of locations, and antibodies to the NK1 receptor (the recepto
r for substance P) labels ICC at the level of the deep muscular plexus
in the small intestine and a subpopulation of enteric neurons in the
large intestine. The presence of neurons in the explants was examined
using antisera to neuron-specific enolase, substance P, and calretinin
. In segments of small and large intestine explanted after the arrival
of neural crest cells, immunoreactive neurons and c-kit- and NK1-immu
noreactive ICC were present with a distribution similar to that seen i
n control tissue at a similar developmental age. In segments of large
intestine explanted before the arrival of neural crest cells, neurons
were not present; however, c-kit-immunoreactive ICC were present in th
ese a neuronal explants, indicating that ICC do not arise from the neu
ral crest. The source of ICC in mammals is therefore likely to be the
mesenchyme of the gut. (C) 1996 Academic Press, Inc.